rs11101535

Variant names:

• chr10-48856386-T-C
• rs11101535
• NM_001394531.1:c.6664-10879T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394531.1(WDFY4):​c.6664-10879T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,010 control chromosomes in the GnomAD database, including 2,702 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2702 hom., cov: 32)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.962
• Publications: 6 publications found

Genes affected

WDFY4 (HGNC:29323): (WDFY family member 4) Predicted to be involved in autophagy. Predicted to act upstream of or within with a positive effect on CD8-positive, alpha-beta T cell activation. Predicted to act upstream of or within antigen processing and presentation and cellular response to virus. Predicted to be located in early endosome and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

WDFY4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDFY4	NM_001394531.1	c.6664-10879T>C		intron_variant	Intron 39 of 61	ENST00000325239.12	NP_001381460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDFY4	ENST00000325239.12	c.6664-10879T>C		intron_variant	Intron 39 of 61	5	NM_001394531.1	ENSP00000320563.5

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24117 AN: 151892 Hom.: 2705 Cov.: 32

Gnomad AFR AF: 0.0438

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.186

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.159 AC: 24102 AN: 152010 Hom.: 2702 Cov.: 32 AF XY: 0.165 AC XY: 12226 AN XY: 74292

African (AFR) AF: 0.0437 AC: 1812 AN: 41492

American (AMR) AF: 0.197 AC: 3011 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 625 AN: 3470

East Asian (EAS) AF: 0.588 AC: 3040 AN: 5170

South Asian (SAS) AF: 0.173 AC: 832 AN: 4822

European-Finnish (FIN) AF: 0.208 AC: 2197 AN: 10556

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11883 AN: 67906

Other (OTH) AF: 0.185 AC: 389 AN: 2108

Alfa AF: 0.169 Hom.: 3818

Bravo AF: 0.156

Asia WGS AF: 0.300 AC: 1043 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.4
DANN	Benign	0.81
PhyloP100		0.96
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11101535; hg19: chr10-50064431;